This project is designed to explore the mechanisms involved in the pathogenesis of pulmonary alveolar proteinosis, a disease characterized by the accumulation of lipoproteineous material within the airways. Previous studies have demonstrated profound defects in phagocytosis in alveolar macrophages that appear "overfed" with lipoproteinaceous debri (1). However, studies of surfactant metabolism convincingly show that alveolar macrophages play only a minor role in surfactant turnover under normal circumstances, which is instead re-utilized by type Ii epithelial cells after secretion (2). In this project, studies will be conducted of the morphological and biochemical features of rat alveolar machrophages and type II epithelial cells in culture. They will include studies of the fate and distribution of 5'-nucleotidase in macrophages and type II epithelial cells as a probe of membrane events during endocytosis. Next the uptake and distribution of flourescent phospholipid analogues will be analyzed in colocalization experiments with 5'-nucleotidase and antibodies directed against lysosomes and golgi complex. Alterations in the uptake and distribution of flourescent phospholipid analogues in type II cells will be analyzed in drug-induced phospholipidosis in rats. And finally, the uptake, distribution, and secretion of flourescently labeled phospholipids by type II cells will be analyzed in colocalization experiments with 5'-nucleotidase and antibodies directed against golgi complex and lysosomes.